[5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine]-3'-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite | 1025783-16-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: [5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine]-3'-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite
• CAS: 1025783-16-7
• 化学式: C₄₃H₅₄N₅O₁₀P
• 分子量: 831.903
• InChiKey: FYNKMLIMLHVWST-FMMLDEGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.56
• 重原子数：
  59.0
• 可旋转键数：
  20.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  175.6
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为产物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine 、 双(二异丙基氨基)(2-氰基乙氧基)膦 在 4,5-二氰基咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以84%的产率得到[5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-(methylamino)-2-oxoethyl]-5-methyluridine]-3'-[(2-cyanoethyl)-N,N-diisopropyl]phosphoramidite
  参考文献：
  名称：

  Comparing In Vitro and In Vivo Activity of 2′-O-[2-(Methylamino)-2-oxoethyl]- and 2′-O-Methoxyethyl-Modified Antisense Oligonucleotides

  摘要：

  A number of 2'-O-modified antisense oligonucleotides have been reported for their potential use in oligonucleotide-based therapeutics. To date, most of the in vivo data has been generated for 2'-O-MOE (2'-O-methoxyethyl)- and 2'-O-Me (2'-O-methyl)-modified ASOs (antisense oligonucleotides). We now report the synthesis and biological activity of another 2'-O-modification, namely 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMA). This modification resulted in an increase in the affinity of antisense oligonucleotides to complementary RNA similar to 2'-O-MOE-modified ASOs as compared to first-generation antisense oligodeoxynucleotides. The ASO modified with 2'-O-NMA reduced expression of PTEN mRNA in vitro and in vivo in a dose-dependent manner similar to 2'-O-MOE modified ASO. Importantly, toxicity parameters such as AST, ALT, organ weights, and body weights were found to be normal similar to 2'-O-MOE ASO-treated animal models. The data generated in these experiments suggest that 2'-O-NMA is a useful modification for potential application in both antisense and other oligonucleotide-based drug discovery efforts.

  DOI：

  10.1021/jm701537z